tt52car19 therapy for b-cell acute lymphoblastic leukaemia (b-all)

Conditions: B Acute Lymphoblastic Leukemia

Summary: pbltt52car19 modified t cells are allogenic engineered human t cells (defined as tt52car19 +tcrαβ-) prepared for the treatment of cd19+ b cell leukaemia. the cells are from healthy adult volunteer donors and are not hla-matched. they have been transduced to express and anti-cd19 chimeric antigen receptor (car19) using a lentiviral vector that also incorporates crispr guides for genome editing of cd52 and trac loci in the presence of transiently provided cas9. recognition by tt52car19 t cells mediates eradication of cd19+ leukaemia and other cd19+ b cells through t cell mediated cytotoxicity. this study aims to apply pbltt52car19 t cells to secure molecular remission in children with relapsed/refractory b-all ahead of programmed allogeneic stem cell transplantation. the cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.


Eligibility criteria:
inclusion criteria: * patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-sct) or refractory (not achieving an initial complete response (cr) after 2 cycles of standard chemotherapy) cd19-positive b-acute lymphoblastic leukaemia * morphologically confirmed with leukemic blasts in the bone marrow or a quantifiable mrd load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) * eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available * estimated life expectancy ≥ 12 weeks * lansky (age \< 16 years at the time of assent/consent) or karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 50 eastern cooperative oncology group ecog performance status \< 2 exclusion criteria: * patients/parents unwilling to undergo a follow-up for 15 years * foreseeable poor compliance to the study procedures * cd19-negative b-cell leukaemia * evidence of disease progression after cytoreduction * uncontrollable cns leukaemia or neurological symptoms defined as cns grade 3 (per national comprehensive cancer national guidelines). patients developing grade 3 cns disease at any time after enrolment will be excluded. * absence of suitable hla matched or mismatched donor * weight \< 6 kgs * presence of donor-specific anti-hla antibodies directed against pbltt52car19 * gvhd requiring systemic therapy * systemic steroid therapy prednisolone \>0.5mg/kg/day * known hypersensitivity to any of the test materials or related compounds * active bacterial, fungal, or viral infection not controlled by a standard of care anti-microbial or anti-viral treatment. uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or anti-fungal therapy. * uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy. * risk of pregnancy or non-compliance with contraception (if applicable). girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion. * lactating female participants unwilling to stop breastfeeding * intrathecal methotrexate within 4 weeks or intrathecal chemotherapy (e.g ara-c) within 2 weeks of lymphodepletion * less than 2 half-lives from prior therapy with immune checkpoint pathway modifiers to lymphodepletion * prior car19 therapy known to be associated with ≥grade 3 cytokine release syndrome (crs) or ≥grade 3 drug-related cns toxicity

Keywords: relapsed refractory